VIP (Vasoactive Intestinal Peptide)

VIP is like a local hero who looked like a lifesaver in a handful of dramatic anecdotes. When finally put through a fair, large-scale audition against a placebo stand-in, it simply did not deliver. It is a real hormone with real biology, just not the rescue treatment the hype promised.

Binds class B G-protein-coupled receptors VPAC1 and VPAC2 (with additional affinity at PAC1), activating Gs/adenylyl cyclase and raising intracellular cAMP. This produces vasodilation, bronchodilation and broad anti-inflammatory and immunomodulatory effects: suppression of TNF-alpha and IL-6, a shift toward regulatory and tolerogenic immune responses, and reported protection of alveolar type II cells. Endogenous VIP is concentrated in the lungs, gut and CNS and has a very short half-life.

Research contexts. Not proven uses, and not recommendations.

Substantial in volume but ultimately unconvincing. VIP is a well-characterised endogenous human hormone and synthetic aviptadil has been through genuine clinical trials. Early, largely uncontrolled COVID-19 data (expanded access and company-sponsored Phase 2b/3) suggested benefit. However, the FDA declined an emergency use authorisation in 2021, and the definitive, independent, NIH-funded randomised placebo-controlled trial (TESICO, 471 patients in the aviptadil comparison, Lancet Respir Med 2023) found no significant benefit and was stopped for futility. Earlier-phase work exists in sarcoidosis and pulmonary hypertension with orphan-drug designations but no full regulatory approval. For the 'recovery', immune-boosting and CIRS uses promoted on the grey market, there is no robust human efficacy evidence.

• !The best-quality human trial (TESICO) was negative and the FDA declined an emergency use authorisation. High-profile COVID recovery claims did not hold up under rigorous testing.
• !Not a licensed medicine in the UK or anywhere else. Aviptadil remains investigational despite orphan-drug designations.
• !Intravenous administration causes vasodilation-related side effects such as hypotension, flushing and diarrhoea. It is not benign.
• !Grey-market VIP (often nasal sprays) is sold as an unlicensed 'research chemical' with no guarantee of identity, purity, sterility or correct peptide sequence.
• !Marketing for CIRS, mould illness and immune support has no approved-medicine-grade evidence.
• !Native VIP has a very short half-life, so claimed sustained systemic effects from unregulated products are biologically questionable.

Not a licensed medicine in the UK. VIP/aviptadil has no MHRA marketing authorisation and is an investigational drug. It has held FDA orphan-drug designations for ARDS and sarcoidosis, but designation is not approval. The FDA declined an emergency use authorisation in 2021. Material sold online as 'VIP peptide' is an unlicensed product typically labelled 'research chemical / not for human consumption' and has not been assessed by the MHRA for safety, quality or efficacy. Supplying or selling it for human medicinal use without authorisation breaches the Human Medicines Regulations 2012.

• NCT04843761· Phase 3· Completed (aviptadil arm stopped for futility; published 2023)

  ACTIV-3b / TESICO: Aviptadil and Remdesivir for Severely Ill Inpatients With COVID-19

  NIH-funded randomised, placebo-controlled trial; 471 patients in the aviptadil comparison (473 enrolled overall); no significant clinical benefit of IV aviptadil to day 90.

• · Phase 2b/3· Completed

  ZYESAMI (RLF-100/aviptadil) Phase 2b/3 programme in critical COVID-19

  Company-sponsored programme that reported early positive signals later not confirmed by the independent TESICO trial; FDA declined an emergency use authorisation in 2021.

1. 01
   Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial, The Lancet Respiratory Medicine (2023)

   Definitive NIH ACTIV-3b/TESICO RCT; 471 patients in the aviptadil comparison; no significant benefit, stopped for futility.

2. 02
   A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure, The Lancet Respiratory Medicine (linked commentary) (2023)

   Accompanying commentary contextualising the negative TESICO result.

3. 03
   Vasoactive intestinal peptide (VIP) and its receptors VPAC1/VPAC2 - physiology, receptor distribution and anti-inflammatory pharmacology (review), PubMed search

   Background reviews on VIP signalling and immunomodulation; descriptive search rather than a single specific identifier.